The invention relates to a method of preparing d,l-phenylalanine (PA) by the aminating catalytic hydrogenation of alkali salts of phenylpyruvic acid to the corresponding salts of phenylalanine.
It is known to prepare d,l-PA by the aminating catalytic hydrogenation of phenylpyruvic acid (abstract in A. Meister, Biochemistry of the Amino Acids, 2nd ed., New York - London 1965). The yield of the aminating hydrogenation with noble metal catalysts amounts, however, to only 62 to 67% of d,l-PA (F. Knoop, H. Oesterlin, Hoppe Seylers Zeitschrift fuer Physiologische Chemie 148, 311 (1925), 170, 187 and 195 (1928), E. Reimann, D. Voss, Arch. Pharm. 309, 983 (1976)).
The necessary purification involves an additional reduction of the yield, so that industrial production of PA from phenylpyruvic acid has not been possible.
The subject matter of the invention is a method of preparing alkali salts of d,l-phenylalanine, which is characterized in that an alkali salt of phenylpyruvic acid is reacted with hydrogenand ammonia at elevated pressure in the presence of a noble metal catalyst of Group VIII of the Periodic Table.
In accordance with the method of the invention, the yields of alkali salt of PA exceed 90% of the theory. The salts of PA have the advantage of making possible numerous reactions, e.g., to the esters, in a more simple manner than the free PA, and they often result in better yields. An additional advantageous possibility is the use of the alkali salts directly for the enzymatic separation of the optical antipodes and isolation of the physiologically valuable 1-phenylaline. In accordance with DE-OS No. 2,741,081, the alkali salts of, for example d,l-PA can be transformed in aqueous solution with ketene to the N-acetylamino acid alkali salts, and to 1-phenylalanine by subsequent enzymatic cleavage. Also, the free d,l-PA is easy to obtain in a known manner. The alkali salts of phenylpyruvic acid are mainly the Na.sup.+, K.sup.+ or Li.sup.+ salts, of which the lithium salts are preferred. The free d,l-PA can be obtained from the salt thereof by acidification of the salt with an acid, e.g., H Cl.
The noble metals of Group VIII of the Periodic Table of the elements can be used as catalysts, namedly Ru, Rh, Pd, Os. Ir and Pt, of which Rh, Pd and Pt are preferred and Pd is greatly preferred.
The noble metal catalyst can be used in its metallic form or deposited on a support. Supported catalysts, especially those on supports such as active charcoal, CaCO.sub.3, Al.sub.2 O.sub.3 or kieselgur, are used preferentially. A greatly preferred form of the method is the use of palladium catalysts on charcoal, which are made commercially by Degussa, Engelhard Ind. GmbH, Hannover, and Doduco et al., in the form of a 3 to 6% palladium, by weight, on charcoal. The pressure is to be between 10 and 200 Bar, preferably between 30 and 100 bar.
The reaction temperature is between 10.degree. and 150.degree. C. preferably between 20.degree. and 80.degree. C. The pressure is at least 300 bar and preferably up to 200 bar with a preferred range of 10 to 100 bar.
Solvents are to be those which are inert under the reaction conditions. Hydrophilic solvents are preferred, because thus the water formed in the reaction is taken up in a homogeneous phase. Preferred solvents are alcohols of the aliphatic or cycloaliphatic series with 1 to about 10 carbon atoms. Methanol, ethanol, cyclohexanol and ethylene glycol are especially preferred. The reaction time can be varied between 2 and 6 hours. The amount of hydrogen is to be at least stoichiometric with respect to the transformation. The reaction pressure is sustained by the input of hydrogen during the reaction, until the end of the reaction is indicated by the fact that no more hydrogen is being consumed. The amount of the ammonia must be at least the stoichiometric amount, and can amount to 1 to 30 times, preferably 10 to 25 times the stoichiometric amount. A still greater excess does not have a negative effect, but it is avoided for economical reasons.
In the working up of the reaction mixture, the catalyst is filtered out and the solid product is obtained by removing the excess ammonia and solvent.
The alkali salts of PA prepared by the method of the invention are valuable chemical intermediates for the production of pharmaceutical products and active substances for the animal feed industry.